During terminal differentiation in chick lens fiber cells the nuclear DNA is degraded in vivo to low molecular weight double stranded molecules (170 base pairs). Evidence indicates that the epithelial cells (which are the source of most of the fiber cells) are normal with regard to their DNA complement. Thus the process of growth and differentiation in this tissue involves the in vivo degradation of DNA from very high molecular weight to very low molecular weight as the cells leave the dividing population and progress along the pathway of fiber differentiation. It is proposed here to study this process at the level of DNA molecules by determining the DNA molecular weights present in central fiber cells (mature fibers), in peripheral fiber cells (immature fibers) and in epithelial cells. The cells of these three portions of tissue are all in a stationary G1 phase so that the sizes determined may be related to a known DNA complement. For comparison with these experiments DNA sizes will be determined for early blastula stage embryos (actively dividing cells). Total nuclear DNA from epithelial cells will be renatured with degraded DNA from mature fibers and immature fibers to determine if degradation is sequence-specific. Also the relative and absolute amounts of DNA degraded during differentiation will be determined. The sizing of DNA molecules in the size range 10 to the 3rd power to 5 times 10 to the 7th power g/mole will be accomplished by gel electrophoresis. For molecules in the size range 5 times 10 to the 7th power to 10 to the 11th power g/mole a newly developed CsCl density gradient technique will be used. The method will be rigorously tested using native, monodisperse E. coli DNA (molecular weight 2.5 times 10 to the 9th power g/mole). The determination of DNA molecular weights in this size range will tell us if degradation occurs via high molecular weight intermediates. It is hoped that the work proposed here will result in very detailed proposals for the organization of DNA in a eucaryotic nucleus.